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Science 336 (6085): 1178-1181

Copyright © 2012 by the American Association for the Advancement of Science

B Cell Receptor Signal Transduction in the GC Is Short-Circuited by High Phosphatase Activity

Ashraf M. Khalil,1 John C. Cambier,3 Mark J. Shlomchik1,2,*

Abstract: Germinal centers (GCs) generate memory B and plasma cells, which are essential for long-lived humoral immunity. GC B cells with high-affinity B cell receptors (BCRs) are selectively expanded. To enable this selection, BCRs of such cells are thought to signal differently from those with lower affinity. We show that, surprisingly, most proliferating GC B cells did not demonstrate active BCR signaling. Rather, spontaneous and induced signaling was limited by increased phosphatase activity. Accordingly, both SH2 domain–containing phosphatase-1 (SHP-1) and SH2 domain–containing inositol 5 phosphatase were hyperphosphorylated in GC cells and remained colocalized with BCRs after ligation. Furthermore, SHP-1 was required for GC maintenance. Intriguingly, GC B cells in the cell-cycle G2 period regained responsiveness to BCR stimulation. These data have implications for how higher-affinity B cells are selected in the GC.

1 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
2 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Integrated Department of Immunology, National Jewish Health and University of Colorado Health Sciences Center, Denver, CO 80206, USA.

* To whom correspondence should be addressed. E-mail: mark.shlomchik{at}

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